Adolescents with chronic hepatitis C might be good candidates for direct-acting antiviral therapy.

Three Japanese adolescents with chronic hepatitis C were treated by direct-acting antivirals (DAAs). No adverse events or laboratory abnormalities were observed during and after DAA therapy, and a sustained virological response was achieved in all cases. The emotional functioning of the patients and their mothers were improved after DAA therapy.

Elevated serum uric acid level was a notable adverse event during combination therapy with sofosbuvir and ribavirin.

AIM: Combination therapy with sofosbuvir and ribavirin (SOF/RBV) has been recently available for chronic hepatitis C patients with genotype 2 (CHG2) in Japan. The domestic phase III clinical trial showed a high antiviral effect with a relatively safe adverse event (AE) profile. Our aim was to report an important AE detected during treatment. METHODS: A prospective multi-institutional study of 12-week combination therapy with SOF/RBV for CHG2 was carried out to evaluate efficacy and safety. RESULTS: The eligible subjects included 142 patients. Out of 50 assessable patients, 16% of the patients were diagnosed with hyperuricemia. The proportions of subjects with grade 1, grade 3, and grade 4 hyperuricemia were 12, 2, and 2%, respectively. Serum uric acid (UA) levels at week 1 of the therapy (W1) were numerically the highest during therapy in patients with hyperuricemia, and the ratio of W1/baseline serum UA levels was significantly higher than that of post-treatment week 4 or 8/baseline serum UA levels in assessable patients. Serum UA levels at W1 were significantly correlated with body mass index. The difference between serum UA levels at W1 and baseline serum UA levels was significantly correlated with the difference between serum creatinine levels at W1 and baseline serum creatinine levels. CONCLUSIONS: Elevated serum UA level was a notable AE associated with SOF/RBV therapy for CHG2. However, because of the small number of subjects, the exact frequency of AEs should be re-evaluated with larger cohorts. We need to remember that elevated serum UA level might develop during the therapy, especially at W1.

Can endoscopic submucosal dissection be safely performed in a smaller specialized clinic?

AIM: To investigate whether endoscopic submucosal dissection (ESD) can be safely performed at small clinics, such as the Shirakawa Clinic. METHODS: One thousand forty-seven ESDs to treat gastrointestinal tumors were performed at the Shirakawa Clinic from April 2006 to March 2011. The efficacy, technical feasibility and associated complications of the procedures were assessed. The ESD procedures were performed by five endoscopists. Sedation was induced with propofol for esophagogastorduodenal ESD. RESULTS: One thousand forty-seven ESDs were performed to treat 64 patients with esophageal cancer (E), 850 patients with gastric tumors (G: 764 patients with cancer, 82 patients with adenomas and four others), four patients with duodenal cancer (D) and 129 patients with colorectal tumors (C: 94 patients with cancer, 21 patients with adenomas and 14 others). The en bloc resection rate was 94.3% (E: 96.9%, G: 95.8%, D: 100%, C: 79.8%). The median operation time was 46 min (range: 4-360 min) and the mean size of the resected specimens was 18 mm (range: 2-150 mm). No mortal complications were observed in association with the ESD procedures. Perforation occurred in 12 cases (1.1%, E: 1 case, G: 9 cases, D: 1 case, C: 1 case) and postoperative bleeding occurred in 53 cases (5.1%, G: 51 cases, D: 1 case, C: 1 case); however, no case required either emergency surgery or blood transfusion. All of the perforations and postperative bleedings were resolved by endoscopic clipping or hemostasis. The other problematic complication observed was pneumonia, which was treated with conservative therapy. CONCLUSION: ESD can be safely performed in a clinic with established therapeutic methods and medical services to address potential complications.

[Cost cut of cancer by a shift in gastric cancer risk screening (serum ABC classification) combined with eradication of H. pylori, and H. pylori test and treatment program in young people].

We estimated the costs and the benefits of a shift strategy of gastric cancer risk screening (ABC stratification) with H. pylori eradication, and H. pylori test and treatment program in young people, comparing with the current barium gastrograph. The combination of serum pepsinogen, assessing atrophic gastritis status, and H. pylori antibody testing allows for ABC risk stratification. The ABC risk screening could greatly reduce screening and treating cost of gastric cancer. The H. pylori test and treatment program could be the most effective primary prevention of not only gastric cancer but H. pylori-related disease, thereby reducing national cost of cancer and healthcare expenditure. The Japanese Government should take the initiative to implement this strategy as soon as possible.

Analysis of colonoscopic perforations at a local clinic and a tertiary hospital.

AIM: To define the clinical characteristics, and to assess the management of colonoscopic complications at a local clinic. METHODS: A retrospective review of the medical records was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic between April 2006 and December 2010. Data obtained from a tertiary hospital in the same region were also analyzed. The underlying conditions, clinical presentations, perforation locations, treatment types (operative or conservative) and outcome data for patients at the local clinic and the tertiary hospital were compared. RESULTS: A total of 10  826 colonoscopies, and 2625 therapeutic procedures were performed at a local clinic and 32  148 colonoscopies, and 7787 therapeutic procedures were performed at the tertiary hospital. The clinic had no perforations during diagnostic colonoscopy and 8 (0.3%) perforations were determined to be related to therapeutic procedures. The perforation rates in each therapeutic procedure were 0.06% (1/1609) in polypectomy, 0.2% (2/885) in endoscopic mucosal resection (EMR), and 3.8% (5/131) in endoscopic submucosal dissection (ESD). Perforation rates for ESD were significantly higher than those for polypectomy or EMR (P < 0.01). All of these patients were treated conservatively. On the other hand, three (0.01%) perforation cases were observed among the 24  361 diagnostic procedures performed, and these cases were treated with surgery in a tertiary hospital. Six perforations occurred with therapeutic endoscopy (perforation rate, 0.08%; 1 per 1298 procedures). Perforation rates for specific procedure types were 0.02% (1 per 5500) for polypectomy, 0.17% (1 per 561) for EMR, 2.3% (1 per 43) for ESD in the tertiary hospital. There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital. The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital. No procedure-related mortalities occurred. Performing closure with endoscopic clipping reduced the C-reactive protein (CRP) titers. The mean maximum CRP titer was 2.9 ± 1.6 mg/dL with clipping and 9.7 ± 6.2 mg/dL without clipping, respectively (P < 0.05). An operation is indicated in the presence of a large perforation, and in the setting of generalized peritonitis or ongoing sepsis. Although we did not experience such case in the clinic, patients with large perforations should be immediately transferred to a tertiary hospital. Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained. CONCLUSION: It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.

Analysis of ABC (D) stratification for screening patients with gastric cancer.

AIM: To evaluate the value of ABC (D) stratification [combination of serum pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric cancer. METHODS: Ninety-five consecutive patients with gastric cancer were enrolled into the study. The serum pepsinogen I (PG I)/pepsinogen II (PG II) and H. pylori antibody levels were measured. Patients were classified into five groups of ABC (D) stratification according to their serological status. Endoscopic findings of atrophic gastritis and histological differentiation were also analyzed in relation to the ABC (D) stratification. RESULTS: The mean patient age was (67.9 ± 8.9) years. Three patients (3.2%) were classified into group A, 7 patients (7.4%) into group A', 27 patients (28.4%) into group B, 54 patients (56.8%) into group C, and 4 patients (4.2%) into group D, respectively. There were only three cases in group A when the patients taking acid proton pump inhibitors and those who had undergone eradication therapy for H. pylori (group A') were excluded. These three cases had mucosal atrophy in the grey zone according to the diagnostic manual of ABC (D) stratification. Histologically, the mean age of the patients with well differentiated adenocarcinoma was significantly higher than that of the patients with poorly differentiated adenocarcinoma (P < 0.05). There were no differences in the pattern of atrophy in the endoscopies between the well differentiated and poorly differentiated groups. CONCLUSION: ABC (D) stratification is a good method for screening patients with gastric cancers. Endoscopy is needed for grey zone cases to check the extent of mucosal atrophy.

Clinical characteristics and treatment for patients presenting with bleeding duodenal varices.

BACKGROUND AND AIM: Bleeding from ectopic varices, including duodenal varices, is uncommon, but it can be difficult to manage. The clinical data of patients diagnosed and treated for duodenal varices were reviewed to investigate the strategy for treatment. METHODS: The present study reviewed the clinical data of 10 patients with duodenal varices (mean age, 58.2 ± 15.6 years) at our associated institutes during the period between January 1996 and December 2008. RESULTS: Nine patients had duodenal varices located in the second portion, whereas in one case they were located in the duodenal bulbus. The underlying diseases included liver cirrhosis in eight patients, and extrahepatic portal vein obstruction in two patients. The lesions were identified with bleeding from varices in eight of 10 patients. Initial hemostasis was achieved in all eight patients. However, among four patients treated endoscopically only, two patients died from rebleeding from varices and two died from hepatic failure resulting from variceal bleeding. Additional interventional radiology (IVR) was used in three patients and additional surgery was carried out in one case. One patient who was treated with balloon-occluded retrograde transvenous obliteration rebled during IVR and died from bleeding. Two patients who underwent double balloon-occluded embolotherapy and one case who had surgery achieved good clinical outcomes. CONCLUSIONS: Although endoscopic treatment is useful for initial hemostasis of hemorrhagic duodenal varices, the patients who underwent additional IVR after endoscopic treatment achieved good outcomes.

Stricture after endoscopic submucosal dissection for early gastric cancers and adenomas.

BACKGROUND AND AIM: Stricture is a complication that may occur after endoscopic submucosal dissection (ESD) of gastric neoplasms. The goal of the present study was to investigate the incidence, risk factors and management of gastric stricture after ESD. METHODS: The medical records of 308 patients who underwent ESD for gastric neoplasms were reviewed. Stricture is defined as having symptoms caused by an obstruction through which a 1-cm diameter endoscopic fiber cannot be passed. RESULTS: Stricture was identified in six of 308 patients (1.9%). Three of the six lesions were located in the prepylorus, two cases in the antrum and one in the cardia. The mean longitudinal distance and the mean area of the resected specimens in the six cases with stricture (7.8 ± 2.0 cm, 34.0 ± 15.8cm(2) , respectively) was significantly larger than in those without stricture (4.5 ± 1.4cm, 12.7 ± 8.3cm(2) , respectively, P<0.01). The ratio of the resected circumference/whole circumference was 83.3±7.5% in those with stricture in comparison to 25.4 ± 16.3% in those without stricture (P<0.01). All six patients underwent endoscopic balloon dilations, and obtained relief from stricture. However, one patient experienced a gastric perforation and recovered following conservative therapy. CONCLUSION: Sub-circumferential resection over 75% of the circumference by ESD in the prepylorus, antrum and cardia is a risk factor for the occurrence of stricture. Early intervention might be considered for this high-risk group to avoid a perforation during balloon dilation.

Endoscopic treatment of rectal carcinoid tumors.

BACKGROUND: Various methods have been reported for the endoscopic treatment of rectal carcinoid tumors. The present study was designed to identify the optimal treatment strategy for an endoscopic resection. METHODS: Forty rectal carcinoid tumors of 38 patients were treated endoscopically. The indication criteria, complete resection rate, selection of treatment, local recurrence, distant metastases, and complications were analyzed. All tumors were estimated to measure 1 cm or less in diameter, without muscular invasion, atypical features, and lymph node metastases to the pararectal region. RESULTS: Complete resection of the lesions was obtained in 75.0% (30/40). The complete resection rates were 20.0% (1/5) by conventional polypectomy, 84.6% (22/26) by a two-channel endoscopic mucosal resection, and 77.8% (7/9) by endoscopic submucosal dissection. The 10 cases that did not show a clear submucosal layer after initial endoscopic treatment received additional endoscopic microwave coagulation therapy. There were no local or distant recurrences in the followed-up periods (median, 6.4 years). No difference was observed in the complete resection rate between two-channel endoscopic mucosal resection and endoscopic submucosal dissection. CONCLUSIONS: Small carcinoid tumors measuring less than 1 cm in diameter can therefore be managed endoscopically with no recurrence or spread. The selection of endoscopic treatment should be made after taking such factors as cost-effectiveness, expertise, and experience into careful consideration.

Elevated plasma resistin concentrations in patients with liver cirrhosis.

BACKGROUND: Resistin, an adipose-derived polypeptide hormone, has been proposed to be a candidate in insulin resistance, although its role in humans remains controversial. Liver cirrhosis (LC) is characterized by an elevated number of circulating proinflammatory cytokines, hyperinsulinemia and insulin resistance. The aim of this study was to determine the plasma resistin levels in patients with LC. METHODS: Resistin levels were determined in 79 patients with LC and in 31 healthy controls. Patients included 34 with Child-Pugh grade A, 30 with Child's B and 15 with Child's C LC. Fasting plasma glucose, fasting plasma insulin, adiponectin, the homeostatic model assessment insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI) and biochemical parameters were also determined. RESULTS: Plasma resistin levels were 7.61 +/- 6.70 ng/mL in the LC patients and 3.38 +/- 1.68 ng/mL in the controls, respectively. The plasma resistin levels were significantly elevated in patients with LC in comparison to the controls (P < 0.01). The plasma resistin levels increased in a stepwise fashion in line with a higher grade according to Child-Pugh classification. Fasting plasma insulin, adiponectin and HOMA-IR index were also significantly elevated in patients with LC in comparison to controls. Inversely, QUICKI significantly decreased in patients with LC. According to Spearman's rank correlation, log resistin showed significantly positive correlation with fasting plasma insulin, log adiponectin, HOMA-IR index, and a negative correlation with QUICKI (P < 0.01). The plasma resistin levels did not correlate with sex, body mass index and fasting plasma glucose levels. CONCLUSION: The plasma resistin levels increased in patients with LC, thus showing a positive correlation with fasting plasma insulin, adiponectin, HOMA-IR index, and a negative correlation with QUICKI. Although a decreased extraction of resistin due to reduced liver function cannot be ruled out, resistin may contribute to insulin resistance in patients with LC. The pathophysiological roles of resistin in LC still require further investigation.

Primary Sjogren's syndrome complicated by bilateral pleural effusion.

Sjogren's syndrome can cause many organic changes, but is rarely accompanied by pleuritis. We report a 65-year-old patient with primary Sjogren's syndrome who developed bilateral pleuritis with moderately large effusions. He was diagnosed as having Sjogren's syndrome, based on xerophthalmia, xerostomia, positive results for anti-Sjogren's syndrome (anti-SS-A/SS-B) antibodies, the Schirmer test and biopsy findings in the minor salivary glands. The pleural fluid was lymphocyte rich and contained high levels of anti-SS-A/SS-B antibodies. There was no evidence of infection, malignancy or other collagen diseases which cause pleuritis. We conclude that this case adds to the eight previously published reports of primary Sjogren's syndrome complicated by pleural effusion.

Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride-induced chronic liver injury.

BACKGROUND/AIMS: Hepatocyte growth factor (HGF) inhibits liver fibrosis induced by carbon tetrachloride (CCl4) in animal models. NK2 is a natural splice variant of HGF, but its in vivo function remains to be elucidated. We investigated the in vivo effects of NK2 on CCl4-induced liver fibrosis. METHODS: NK2 transgenic mice and wild-type (WT) mice were injected intraperitoneally with CCl4 twice a week. The extent of hepatic fibrosis was evaluated by Azan-Mallory staining. Expression levels of mRNAs of transforming growth factor-beta1 (TGF-beta1) and matrix metalloproteinase-13 (MMP-13) were examined by real-time polymerase chain reaction. The protein levels of alpha-smooth muscle actin (alpha-SMA), c-Met and its phosphorylation were determined by Western blot analysis. RESULTS: Liver fibrosis was significantly more severe in NK2 transgenic mice than in WT mice. CCl4 administration increased the expression levels of TGF-beta1 mRNA and alpha-SMA protein, and decreased the expression of MMP-13 mRNA in livers of NK2 transgenic mice compared with those of WT mice. c-Met protein expression in the liver was compatible with the degree of fibrosis. As for c-Met activation, no difference was found between NK2 and WT livers. CONCLUSION: Overexpression of NK2 acts as an antagonist of HGF and promotes liver fibrosis in CCl4-induced chronic liver injury.

Endoscopic management of duodenal diverticular bleeding.

BACKGROUND: Although the presence of a duodenal diverticulum is usually asymptomatic, bleeding in this tissue is sometimes difficult to diagnose and treat. OBJECTIVE: To investigate the strategy for treatment, we reviewed the clinical data of patients diagnosed and treated for duodenal diverticular bleeding. DESIGN: Retrospective case series. SETTING: Single tertiary-referral center. PATIENTS: Seven consecutive patients with bleeding from a duodenal diverticulum (mean age, 73.7 +/- 3.4 years old). INTERVENTIONS: The clinical characteristics, endoscopic findings, and treatment strategy for duodenal diverticular bleeding. MAIN OUTCOME MEASUREMENTS: All 7 patients achieved hemostasis. Six of 7 patients were treated endoscopically. There were no complications with endoscopic treatment. RESULTS: Three patients bled from diverticula located at the second portion of the duodenum, and 4 patients bled from that located at the third portion. In 6 of 7 patients, lesions were identified and treated endoscopically with hemoclips, hypertonic saline solution and epinephrine (HSE), and/or 1% polidocanol injection. In 1 case, the lesion could not be detected during the first endoscopic examination, and the patient, therefore, was treated with transarterial embolization followed by surgical resection. LIMITATIONS: This preliminary case series described the feasibility of the endoscopic treatment. However, optimal management, including angiography and/or surgery, should be individualized to the patients, location, and type of hemorrhage. CONCLUSIONS: Bleeding from a duodenal diverticulum should be considered in the case of upper-GI bleeding of unknown origin. An endoscopy may be an effective alternative to surgery in the management of a bleeding duodenal diverticulum.

Primary liver cancers with nonalcoholic steatohepatitis.

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.

Hepatocellular carcinoma with portal vein tumor thrombosis: clinical characteristics, prognosis, and patient survival analysis.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a poor prognosis. New therapeutic modalities, such as continuous hepatic arterial infusion chemotherapy (CHAIC), have recently been reported to be promising strategies. The aim of this study was to evaluate the clinical characteristics, prognosis, and survival of patients with PVTT according to treatment regimen. One hundred ninety-three patients with HCC complicated with PVTT at the time of diagnosis were included in this study. All patients were newly diagnosed to have HCC and were observed from January 1992 to December 2003. CHAIC was performed using an implanted drug delivery system with low-dose cisplatin and 5-fluorouracil. Clinical characteristics, prognosis, and patient survival were analyzed by the Kaplan-Meier method and Cox's proportional hazards model. The mean age of the patients complicated with PVTT was 64.3+/-10.3 years (range, 20-88 years). The survival of the 193 patients with PVTT was 37.5%, 24.0%, 18.9%, and 8.3% at 1, 2, 3, and 5 years, respectively. According to treatment, the survival of patients who underwent surgical treatment was the best, followed by CHAIC, transcatheter arterial infusion/embolization, and supportive care. The 3-year survivals for each treatment regimen were 53.0%, 19.3%, 15.0%, and 4.0%, respectively. Although the survival of patients who received surgical treatment was best, such patients were restricted. There was no difference in survival between treated and untreated patients demonstrating Child-Pugh grade C. In Child B patients, treatment for HCC significantly increased survival (P<0.01). Cox's proportional hazards model revealed the Child-Pugh classification to be an independent prognostic factor for patients with HCC and PVTT (P<0.01). We conclude that the prognosis of HCC with PVTT was quite poor. The treatment did not improve the survival of Child C patients. As a result, the prevention, early diagnosis, and development of new treatment strategies are required.

HGF ameliorates a high-fat diet-induced fatty liver.

Hepatocyte growth factor (HGF) has various effects especially on epithelial cells. However, the precise role of HGF on lipogenesis is still not fully understood. A high-fat diet was administered to HGF transgenic mice and wild-type control mice in vivo. Furthermore, recombinant human HGF (rhHGF) was administered to HepG2 cell line in vitro. We performed an analysis regarding the factors relating to lipid metabolism. An overexpression of HGF dramatically ameliorates a high-fat diet-induced fatty liver. HGF transgenic mice showed an apparently reduced lipid accumulation in the liver. The activation of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (ApoB) accompanying higher triglyceride levels in the serum were found in HGF transgenic mice on a normal diet. Interestingly, this upregulation of the MTP activation became more apparent in the high-fat diet. In addition, the administration of rhHGF stimulated MTP and ApoB expression while reducing reduced the intracellular lipid content in HepG2 cell line. However, this induction of MTP and ApoB by HGF was clearly inhibited by PD98059 (MAPK inhibitor). In conclusion, the data presented in this study indicated that HGF ameliorates a high-fat diet-induced fatty liver via the activation of MTP and ApoB.

Hepatocellular carcinoma in young adults: the clinical characteristics, prognosis, and findings of a patient survival analysis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20-39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.

Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection.

BACKGROUND: Despite the progression of therapeutic approaches, a high frequency of recurrence is what determines the long-term prognosis of patients with hepatocellular carcinoma (HCC). In this study, the chemopreventive effects of vitamin K2 on the recurrence and survival of patients with HCC after curative therapy were evaluated. METHODS: Sixty patients who were diagnosed to be free of HCC after radiofrequency ablation therapy or surgery were randomly assigned to either the vitamin K2 group (n = 30 patients) or the control group (n = 30 patients). All patients were positive for the hepatitis C virus (HCV) antibody and hepatitis B surface antigen positive patients were excluded from this study. Patients in the vitamin K2 group received an oral dose of menatetrenone at 45 mg per day. Disease recurrence and the survival rates were analyzed in patients with HCC. RESULTS: The cumulative recurrence-free rates in the vitamin K2 group were 92.3% at 12 months, 48.6% at 24 months and 38.8% at 36 months; and those in the control group were 71.7%, 35.9% and 9.9%, respectively (P = 0.045). The cumulative survival rates in the vitamin K2 group were 100% at 12 months, 95.0% at 24 months and 77.5% at 36 months; and those in the control group were 95.8%, 90.2% and 66.4%, respectively (P = 0.70). CONCLUSIONS: Vitamin K2 may have a suppressive effect on the recurrence of HCC and a beneficial effect on tumor recurrence. However, there was no significant difference in the survival rates. The chemopreventive effects of vitamin K2 are not sufficient. The development of a further regimen such as combination therapy is required.

Hepatocyte growth factor accelerates thrombopoiesis in transgenic mice.

Hepatocyte growth factor (HGF) is one of the potent growth factors for liver regeneration and has a strong effect on epithelial and nonepithelial cells. As one of the pleiotropic functions, HGF acts as a hematopoietic regulator in the proliferation and differentiation of hematopoietic progenitors. However, the effect of HGF on the thrombopoietic function remains unclear. The correlation between HGF and thrombopoiesis was investigated in transgenic (TG) mice overexpressing murine HGF controlled by the murine HGF by the metallothionein promoter. Furthermore, the mechanism of thrombocytosis induced by HGF in vitro was analyzed in hepatoma cell line HepG2. Both the platelet count and the serum thrombopoietin (TPO) concentration were significantly higher in TG than in the wild type (WT) control mice. In the liver and spleen, the expression of TPOmRNA in TG was higher than that in WT by real-time polymerase chain reaction. The expressions of transcriptional factor of TPO, GABP-alpha/beta were more increased in TG liver compared to WT. In an in vitro study, HGF induced TPO and GABP-alpha/beta expression and enhanced TPO promoter activity. Therefore, HGF induced thrombopoiesis accompanied with the overexpression of TPO through GABP stimulation.